Taxol, cisplatin and vincristine are all promising anti-tumor drugs. Unfortunately, these drugs have the adverse side effects of toxic sensory or sensorimotor neuropathy and neuronal dysfunction. For example, taxol is a plant alkaloid that promotes the assembly of microtubules and stabilizes them. Clinical trials have demonstrated taxol's antineoplastic activity against solid tumors, such as metastatic melanoma. However, taxol causes toxic sensory neuropathy and is cytotoxic to dorsal root ganglion neurons in vitro. When explants of dorsal root ganglion (DRG) attached to the spinal cord are exposed to taxol, unusual arrays of microtubules are formed in neurons and supporting cells, and DRG neurons die. Neuropathies have also resulted when cisplatin or vincristine have been used to treat tumors.
Dideoxycytidine (ddc) and dideoxyinosine (ddI) are anti-viral agents currently being tested in the treatment of AIDS. These agents also have the side effect of toxic neuropathy.
Co-treatment with the neuronotrophic factor, nerve growth factor (NGF), has previously been shown to prevent neuronal death in in vitro experiments (Peterson and Crain, Science, 217: 377 (1982)). However, it has been entirely unclear whether the growth factor could preserve normal neuronal function after toxic insults.
The method in the present invention solves the problems of toxic neuropathy and neuronal dysfunction. The method of the present invention involves coadministration of neuronotrophic factors with these anti-tumor and anti-viral agents. Such coadministration results in both the treatment of tumors and viruses, and in the prevention of toxic neuropathy.